Plot Survival vs Guan score

Risk prediction summary by quality of model

Summary statistics by subtype

true and false positive percentages
TPR
FPR
subtype low high/extreme extreme low high/extreme extreme
FGFR3 88.0 86.0 80.0 12.00 14.0 20.00
t(4;14) 87.5 85.7 90.9 12.50 14.3 9.09
del1p 97.0 36.0 29.0 3.00 64.0 71.00
amp1q 94.0 64.0 53.0 6.00 36.0 47.00
del13 98.0 46.0 54.0 2.00 54.0 46.00
agnostic 92.5 31.8 19.7 7.45 68.2 80.30

SYGNAL risk prediction for each subject was chosen based on the quality of the subtypes each subject exhibited. If a subject exhibited multiple subtypes then the average of the best quality models risk prediction was used to classify the subject. If no subtypes were exhibited then the “all” model was used. For example, if a subject exhibited the t(4;14), amp1q, and del(1p) subtypes then the t(4;14) subdtype risk prediction would be used for that subject.

subtype AUC quality
FGFR3 0.932 A
t(4;14) 0.918 A
del(13) 0.890 B
del(1p) 0.878 B
amp(1q) 0.843 B
agnostic 0.724 C
subtype AUC sky92 gep70 n quality
FGFR3 0.932 0.661 0.779 77 A
t(4;14) 0.918 0.670 0.745 105 A
del(1p) 0.890 0.614 0.616 60 B
amp(1q) 0.878 0.655 0.736 203 B
del(13) 0.843 0.674 0.737 190 B
agnostic 0.724 0.615 0.648 769 C

IA12

Scatter plots by subtype

ia12 PFS cors
subtype mmSYGNAL SKY92 GEP70
t(4;14) -0.068 -0.243 -0.158
FGFR3 0.069 -0.255 -0.123
amp(1q) -0.166 -0.219 -0.350
del(1p) -0.077 -0.188 -0.181
del(13) -0.057 -0.291 -0.307
agnostic -0.056 -0.293 -0.244
ia12 Guan cors
subtype mmSYGNAL SKY92 GEP70
t(4;14) 0.332 0.261 0.304
FGFR3 0.500 0.335 0.490
amp(1q) 0.597 0.280 0.469
del(1p) 0.541 0.262 0.448
del(13) 0.648 0.301 0.559
agnostic 0.624 0.372 0.506

Full model: highest quality

50% survival probability PFS (months)
methods extreme high low
SYGNAL 18.4 27.4 39.9
GEP70 NA 20.0 40.5
SKY92 NA 15.8 39.1
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

t(4;14)

50% survival probability PFS (months)
methods extreme high low
SYGNAL 20 22.1 45.2
GEP70 NA 13.1 29.6
SKY92 NA 12.4 29.6
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

FGFR3

50% survival probability PFS (months)
methods extreme high low
SYGNAL 20.4 23.6 59.0
GEP70 NA 13.1 29.0
SKY92 NA 12.4 28.2
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

del(1p)

50% survival probability PFS (months)
methods extreme high low
SYGNAL 9.915 5.9 NA
GEP70 NA 13.0 NA
SKY92 NA 9.7 NA
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

del(13)

50% survival probability PFS (months)
methods extreme high low
SYGNAL 11.4 21.3 44.3
GEP70 NA 20.0 32.6
SKY92 NA 15.0 31.7
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

amp(1q)

50% survival probability PFS (months)
methods extreme high low
SYGNAL 15 20.8 45.2
GEP70 NA 16.6 42.0
SKY92 NA 18.4 39.2
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

agnostic

50% survival probability PFS (months)
methods extreme high low
SYGNAL 11.3 23.9 41.3
GEP70 NA 20.0 40.5
SKY92 NA 15.8 39.1
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

Subtype specific models

Quality models

50% survival probability PFS (months)
quality extreme high low
A 20.0 20.8 45.2
B 14.2 23.6 45.2
C 11.3 23.9 41.3
50% survival probability PFS
n
quality extreme high low extreme high low
A 20.0 20.8 45.2 37 10 59
B 14.2 23.6 45.2 37 31 257
C 11.3 23.9 41.3 37 90 642

Best quality model

GSE19784

Scatter plots by subtype

GSE19784 Guan cors
method correlation
mmSYGNAL 0.276
SKY92 0.537
GEP70 0.388
GSE19784 PFS cors
method correlation
mmSYGNAL -0.275
SKY92 -0.529
GEP70 -0.379

Full model: all subjects

Full model ROC (first plot) uses all subjects with SYGNAL using the best quality model.

Med PFS 50% (months)
methods extreme high low
SYGNAL 8.845 20.740 31.517
GEP70 NA 6.253 30.602
SKY92 NA 3.355 28.873
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

t(4;14)

t(4;14) ROC curve only shows the risk prediction for subjects exhibiting the t(4;14) subtype.

Med PFS 50% (months)
methods extreme high low
SYGNAL 14.03 4.982 NA
GEP70 NA 7.930 30.093
SKY92 NA 7.930 30.093
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

GSE24080

Scatter plots by subtype

GSE24080 Guan cors
method correlation
mmSYGNAL 0.332
SKY92 0.335
GEP70 0.338
GSE24080 PFS cors
method correlation
mmSYGNAL -0.287
SKY92 -0.288
GEP70 -0.371

Compare Guan to survival clinical outcome

Risk stratification by genetic abnormality subtype counts

Risk stratification by genetic abnormality subtype was done by first calculating the number of high risk subtypes (del(17p), 1q+, FGFR3, WHSC1 and MAF) each subject showed. All subjects were then ranked by number of subtypes (0 to 6). For each subtype count category, subjects were randomly ordered.

Rank ordering within each subtype count category was based on SYGNAL risk probability for the stratification that combined SYGNAL risk probability and subtype stratification.

Cytogenetics: change risk distribution

IA12 cytogenetics
cyto count total high low
0 456 35% 65%
>0 313 40% 60%
1 194 38% 62%
2 81 40% 60%
3 33 55% 45%
4 5 40% 60%

Sample sizes of number of mutations
mutations counts
4 5
3 33
2 81
1 194
0 456

KM survival plots

Risk stratification by subtype abnormality counts

del(13) and MAF subtypes are not included in subtype abnormality counts.

Table of log rank test for difference of survival curves for subjects with 0 abnormalities vs those with 1 to 5 abnormalities.

log rank p-values
count p
1 0.660
2 0.281
3 0.033
4 0.448
0 v 1+ 0.170
50% survival probability PFS (months)
abnormalities 50% PFS n
4 12.7 5
3 23.8 33
2 30.1 81
1 32.6 194
0 39.1 456

KM plots cyto vs mmSYGNAL

Full model: all subjects

Full model ROC (first plot) uses all subjects with SYGNAL using the best quality model.

50% survival probability PFS (months)
methods extreme high low
SYGNAL 12.064 28.653 74.149
GEP70 NA 20.842 74.149
SKY92 NA 22.333 74.589
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

t(4;14)

t(4;14) ROC curve only shows the risk prediction for subjects exhibiting the t(4;14) subtype.

50% survival probability PFS (months)
methods extreme high low
SYGNAL 12.268 31.042 NA
GEP70 NA 16.063 NA
SKY92 NA 13.657 64.084
logrank FDR values
risk mmSYGNAL GEP70 SKY92
extreme NA NA NA
high 0 0 0

Full plots

ROC

Highest quality model

t(4;14)

KM

Highest quality model

highest quality model
IA12
GSE19784
GSE24080
methods extreme high low extreme high low extreme high low
SYGNAL 18.4 27.4 39.9 8.85 20.70 31.5 12.1 28.7 74.1
GEP70 NA 20.0 40.5 NA 6.25 30.6 NA 20.8 74.1
SKY92 NA 15.8 39.1 NA 3.36 28.9 NA 22.3 74.6
IA12
GSE19784
GSE24080
methods extreme low high low high low high
mmSYGNAL 628 68 73 233 49 474 85
GEP70 608 0 161 205 77 503 56
SKY92 673 0 96 278 4 547 12

t(4;14)

t(4;14)
IA12
GSE19784
GSE24080
methods extreme high low extreme high low extreme high low
SYGNAL 20 22.1 45.2 14.03 4.982 NA 12.268 31.042 NA
GEP70 NA 13.1 29.6 NA 7.930 30.093 NA 16.063 NA
SKY92 NA 12.4 29.6 NA 7.930 30.093 NA 13.657 64.084

Summary: predicted risk class

risk
IA12
GSE19784
GSE24080
clinical predicted mmSYGNAL GEP70 SKY92 mmSYGNAL GEP70 SKY92 mmSYGNAL GEP70 SKY92
extreme extreme 17 0 0 4 0 0 8 0 0
extreme high 8 29 23 8 12 8 5 15 18
extreme low 46 42 48 28 28 32 30 28 25
high extreme 33 0 0 7 0 0 9 0 0
high high 26 65 33 21 9 3 28 35 40
high low 156 150 182 94 113 119 75 77 72
low extreme 18 0 0 0 0 0 4 0 0
low high 39 67 40 9 1 0 31 27 41
low low 426 416 443 111 119 120 369 377 363
method IA12 GSE19784 GSE24080
mmSYGNAL 0 0 0
GEP70 0 0 0
SKY92 0 0 0

ROC mmSYGNAL